Session: 114. Sickle Cell Disease, Sickle Cell Trait, and Other Hemoglobinopathies, Excluding Thalassemias: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Sickle Cell Disease, Clinical Research, Hemoglobinopathies, Diseases, Immune mechanism, Patient-reported outcomes, Technology and Procedures, Study Population, Human, Imaging
Methods: We examined whole-brain group differences in evoked-pain FC between the S1 leg area and DMN in adult SCD patients aged18-73 (n = 18 total, n=11 females) compared to matched healthy controls (HCs, n = 16). Participants underwent fMRI scans during tonic pressure pain stimulation applied via a computerized cuff on the left gastrocnemius muscle. We selected the S1 leg area and DMN as primary seed regions, and seed-to-whole-brain connectivity maps were constructed to analyze group differences in FC. Pressure pain tolerance (PPTol) was assessed at the dominant-side upper trapezius muscle, providing an experimental measure of pain sensitivity (higher PPTol suggests lower pain sensitivity). Clinical pain outcomes included the Brief Pain Inventory (BPI) Pain Severity, Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity, and PROMIS Pain Interference scores. The impact of SCD and pain on QoL was measured using the Pediatric Quality of Life Inventory (PedsQLTM) SCD module (adult version), with higher scores indicating better QoL and fewer pain-related difficulties. Pearson correlations were computed between FC and these clinical measures in SCD patients to explore the relationship between brain connectivity and pain perception and management.
Results: SCD patients exhibited reduced FC during the pressure pain stimulation between the left S1 leg area and the thalamus, both left (T=3.37, pFWE=0.04) and right (T=3.37, pFWE=0.03) hemispheres, compared to HCs. Additionally, individuals with SCD showed reduced FC between the DMN and the right prefrontal cortex (PFC) (T=3.37, pFWE<0.01) compared to HCs. In SCD, the FC between the DMN and right PFC showed a marginal negative correlation with PPTol (r=-0.46, p=0.06), indicating that decreased FC was associated with increased pain tolerance. Reduced FC between the DMN and right PFC was also associated with lower levels of clinical pain: BPI Pain Severity (r=0.60, p=0.012), PROMIS Pain Intensity (r=0.70, p<0.01), and PROMIS Pain Interference scores (r=0.62, p=0.01) in SCD. A negative association was found between FC in the same regions and PedsQL scores (r=-0.78, p<0.001), indicating that decreased FC was linked to greater QoL in SCD.
Conclusions: Our results demonstrate altered FC in SCD patients compared to HCs, with differences observed in regions implicated in pain processing. The unexpected direction of the correlations, where patients exhibited reduced FC compared to controls, despite increased FC being linked to worse pain outcomes, implicates different underlying pain pathways. The reduced FC between the S1 leg area and thalamus might be related to descending pathways resulting from recurrent VOCs and chronic opioid use, which are common in SCD patients. Concurrently, the decreased FC between the DMN and PFC may reduce cognitive focus on pain, potentially increasing pain tolerance. Our findings are novel but must be validated through our continuous investigation with a larger sample size. Potential confounders such as chronic transfusion, hydroxyurea, and other concurrent treatments for managing pain may also impact the FC and should be explored in future studies. Neuroimaging techniques such as fMRI are important tools for advancing the understanding of pain mechanisms and facilitating diagnostics, prognostics, and pain management outcomes in SCD.
Disclosures: No relevant conflicts of interest to declare.